Common gene-network signature of different neurological disorders and their potential implications to neuroAIDS.
Common gene-network signature of different neurological disorders and their potential implications to neuroAIDS.
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DOI：
10.1371/journal.pone.0181642
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Nair M
中科院分区：
文献类型：
--
作者：
Sagar V;Pilakka-Kanthikeel S;Martinez PC;Atluri VSR;Nair M
在人类免疫缺陷病毒（HIV）感染期间的AIDS（neuroAIDS）的神经系统并发症被非特异性的、多方面的神经系统病症所困扰，因此，在分子水平上为这种神经系统复杂性定义特定的诊断/治疗机制仍然是难以捉摸的。使用基于计算机的整合基因网络分析，我们发现HIV感染与本研究中选择的12种神经系统疾病中的每一种都共享收敛基因网络。重要的是，在艾滋病毒感染、阿尔茨海默病、帕金森病、多发性硬化症和老年黄斑变性中发现了一个共同的基因网络。在HIV感染的单核细胞中的mRNA微阵列分析显示，该计算机衍生的共同途径的几个基因的表达发生了显著变化，这表明该基因电路在驱动neuroAIDS病症中可能具有生理相关性。此外，将这种独特的基因网络与另一种计算机衍生的新的会聚基因网络进行比较，所述会聚基因网络由七种主要神经系统疾病（阿尔茨海默病、帕金森病、多发性硬化症、老年黄斑变性、肌萎缩性侧索硬化症、血管性痴呆和不宁腿综合征）共享。这些网络的基因电路不同，但是，在大的，它们涉及先天免疫信号通路，这表明不同的神经发病机制的免疫学基础的共性。这里报道的共同基因电路可以提供一个前瞻性的平台，以了解属于其他神经疾病的基因电路如何在实时neuroAIDS条件下进行卷积，它可以阐明HIV感染和neuroAIDS风险之间的潜在和迄今未知的遗传重叠。此外，它可能导致理解疾病进展，识别生物标志物和开发治疗方法的新范式。
The neurological complications of AIDS (neuroAIDS) during the infection of human immunodeficiency virus (HIV) are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s) for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and age macular degeneration. An mRNA microarray analysis in HIV-infected monocytes showed significant changes in the expression of several genes of this in silico derived common pathway which suggests the possible physiological relevance of this gene-circuit in driving neuroAIDS condition. Further, this unique gene network was compared with another in silico derived novel, convergent gene network which is shared by seven major neurological disorders (Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis, Age Macular Degeneration, Amyotrophic Lateral Sclerosis, Vascular Dementia, and Restless Leg Syndrome). These networks differed in their gene circuits; however, in large, they involved innate immunity signaling pathways, which suggests commonalities in the immunological basis of different neuropathogenesis. The common gene circuits reported here can provide a prospective platform to understand how gene-circuits belonging to other neuro-disorders may be convoluted during real-time neuroAIDS condition and it may elucidate the underlying–and so far unknown–genetic overlap between HIV infection and neuroAIDS risk. Also, it may lead to a new paradigm in understanding disease progression, identifying biomarkers, and developing therapies.
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